High-definition tDCS over primary motor cortex modulates brain signal variability and functional connectivity in episodic migraine.

Objective: This study investigated how high-definition transcranial direct current stimulation (HD-tDCS) over the primary motor cortex (M1) affects brain signal variability and functional connectivity in the trigeminal pain pathway, and their association with changes in migraine attacks.

Methods: Twenty-five episodic migraine patients were randomized for ten daily sessions of active or sham M1 HD-tDCS. Resting-state blood-oxygenation-level-dependent (BOLD) signal variability and seed-based functional connectivity were assessed pre- and post-treatment.

Exploring HD-tDCS Effect on μ-opioid Receptor and Pain Sensitivity in Temporomandibular Disorder: A Pilot Randomized Clinical Trial Study.

This study explored the association between experimentally-induced pain sensitivity and µ-opioid receptor (μOR) availability in patients with temporomandibular disorder (TMD) and further investigated any changes in the pain and μOR availability following high-definition transcranial direct current stimulation (HD-tDCS) over the primary motor cortex (M1) with pilot randomized clinical trials. Seven patients with TMD completed either active (n = 3) or sham treatment (n = 4) for 10 daily sessions and underwent positron emission tomography (PET) scans with [C]carfentanil, a selective μOR agonist, a week before and after treatment. PET imaging consisted of an early resting and late phase with the sustained masseteric pain challenge by computer-controlled injection of 5% hypertonic saline.

Effect of High-Definition Transcranial Direct Current Stimulation on Headache Severity and Central µ-Opioid Receptor Availability in Episodic Migraine.

Objective: The current understanding of utilizing HD-tDCS as a targeted approach to improve headache attacks and modulate endogenous opioid systems in episodic migraine is relatively limited. This study aimed to determine whether high-definition transcranial direct current stimulation (HD-tDCS) over the primary motor cortex (M1) can improve clinical outcomes and endogenous µ-opioid receptor (µOR) availability for episodic migraineurs.

Methods: In a randomized, double-blind, and sham-controlled trial, 25 patients completed 10-daily 20-min M1 HD-tDCS, repeated Positron Emission Tomography (PET) scans with a selective agonist for µOR.

Classifying migraine using PET compressive big data analytics of brain's -opioid and D2/D3 dopamine neurotransmission.

Migraine is a common and debilitating pain disorder associated with dysfunction of the central nervous system. Advanced magnetic resonance imaging (MRI) studies have reported relevant pathophysiologic states in migraine. However, its molecular mechanistic processes are still poorly understood .

Management of Episodic Migraine with Neuromodulation: A Case Report.

Migraine is a highly prevalent neurovascular disorder that affects approximately 15% of the global population. Migraine attacks are a complex cascade of neurologic events that lead to debilitating symptoms and are often associated with inhibitory behavior. The constellation of severe signs and symptoms during the ictal phase (headache attack) makes migraine the third most common cause of disability globally in both sexes under the age of 50.

Brain Mechanisms of Virtual Reality Breathing Versus Traditional Mindful Breathing in Pain Modulation: Observational Functional Near-infrared Spectroscopy Study.

Background: Pain is a complex experience that involves sensory-discriminative and cognitive-emotional neuronal processes. It has long been known across cultures that pain can be relieved by mindful breathing (MB). There is a common assumption that MB exerts its analgesic effect through interoception.

Functional Magnetic Resonance Imaging Signal Variability Is Associated With Neuromodulation in Fibromyalgia.

Objectives: Although primary motor cortex (M1) transcranial direct current stimulation (tDCS) has an analgesic effect in fibromyalgia (FM), its neural mechanism remains elusive. We investigated whether M1-tDCS modulates a regional temporal variability of blood-oxygenation-level-dependent (BOLD) signals, an indicator of the brain's flexibility and efficiency and if this change is associated with pain improvement.

Materials And Methods: In a within-subjects cross-over design, 12 female FM patients underwent sham and active tDCS on five consecutive days, respectively.

Shedding light on pain for the clinic: a comprehensive review of using functional near-infrared spectroscopy to monitor its process in the brain.

Pain is a complex experience that involves sensation, emotion, and cognition. The subjectivity of the traditional pain measurement tools has expedited the interest in developing neuroimaging techniques to monitor pain objectively. Among noninvasive neuroimaging techniques, functional near-infrared spectroscopy (fNIRS) has balanced spatial and temporal resolution; yet, it is portable, quiet, and cost-effective.

Dopaminergic Regulation of Reward System Connectivity Underpins Pain and Emotional Suffering in Migraine.

Purpose: It has been suggested that reward system dysfunction may account for emotion and pain suffering in migraine. However, there is a lack of evidence whether the altered reward system connectivity is directly associated with clinical manifestations, including negative affect and ictal pain severity and, at the molecular level, the dopamine (DA) D2/D3 receptors (D2/3Rs) signaling implicated in encoding motivational and emotional cues.

Patients And Methods: We acquired resting-state functional MRI from interictal episodic migraine (EM) patients and age-matched healthy controls, as well as positron emission tomography (PET) with [C]raclopride, a selective radiotracer for DA D2/3Rs, from a subset of these participants.

Differential alteration of fMRI signal variability in the ascending trigeminal somatosensory and pain modulatory pathways in migraine.

Background: The moment-to-moment variability of resting-state brain activity has been suggested to play an active role in chronic pain. Here, we investigated the regional blood-oxygen-level-dependent signal variability (BOLD) and inter-regional dynamic functional connectivity (dFC) in the interictal phase of migraine and its relationship with the attack severity.

Methods: We acquired resting-state functional magnetic resonance imaging from 20 migraine patients and 26 healthy controls (HC).

Sensory-Discriminative Three-Dimensional Body Pain Mobile App Measures Versus Traditional Pain Measurement With a Visual Analog Scale: Validation Study.

Background: To quantify pain severity in patients and the efficacy treatments, researchers and clinicians apply tools such as the traditional visual analog scale (VAS) that leads to inaccurate interpretation of the main sensory pain.

Objective: This study aimed to validate the pain measurements of a neuroscience-based 3D body pain mobile app called GeoPain.

Methods: Patients with temporomandibular disorder (TMD) were assessed using GeoPain measures in comparison to VAS and positive and negative affect schedule (PANAS), pain and mood scales, respectively.

Impact of chronic migraine attacks and their severity on the endogenous μ-opioid neurotransmission in the limbic system.

Objective: To evaluate, in vivo, the impact of ongoing chronic migraine (CM) attacks on the endogenous μ-opioid neurotransmission.

Background: CM is associated with cognitive-emotional dysfunction. CM is commonly associated with frequent acute medication use, including opioids.

Feasibility of a Real-Time Clinical Augmented Reality and Artificial Intelligence Framework for Pain Detection and Localization From the Brain.

Background: For many years, clinicians have been seeking for objective pain assessment solutions via neuroimaging techniques, focusing on the brain to detect human pain. Unfortunately, most of those techniques are not applicable in the clinical environment or lack accuracy.

Objective: This study aimed to test the feasibility of a mobile neuroimaging-based clinical augmented reality (AR) and artificial intelligence (AI) framework, CLARAi, for objective pain detection and also localization direct from the patient's brain in real time.

Dopamine D2/D3 imbalance during migraine attack and allodynia in vivo.

Objective: To evaluate in vivo the dynamics of endogenous dopamine (DA) neurotransmission during migraine ictus with allodynia.

Methods: We examined 8 episodic migraineurs and 8 healthy controls (HC) using PET with [C]raclopride. The uptake measure of [C]raclopride, nondisplaceable binding potential (BP), would increase when there was a reduction in endogenous DA release.

Feasibility of Non-invasive Brain Modulation for Management of Pain Related to Chemoradiotherapy in Patients with Advanced Head and Neck Cancer.

Patients with head and neck cancer often experience a significant decrease in their quality of life during chemoradiotherapy (CRT) due to treatment-related pain, which is frequently classified as severe. Transcranial direct current stimulation (tDCS) is a method of non-invasive brain stimulation that has been frequently used in experimental and clinical pain studies. In this pilot study, we investigated the clinical impact and central mechanisms of twenty primary motor cortex (M1) stimulation sessions with tDCS during 7 weeks of CRT for head and neck cancer.

Changes in resting state functional connectivity after repetitive transcranial direct current stimulation applied to motor cortex in fibromyalgia patients.

Background: Fibromyalgia (FM) is a chronic, centralized pain condition characterized by alterations in the functional, chemical, and structural brain networks responsible for sensory and mood processing. Transcranial direct current stimulation (tDCS) has emerged as a potential treatment for FM. tDCS can alter functional connectivity (FC) in brain regions underneath and distant to the stimulating electrode, although the analgesic mechanisms of repetitive tDCS remain unknown.

High-Definition and Non-invasive Brain Modulation of Pain and Motor Dysfunction in Chronic TMD.

Background: Temporomandibular disorders (TMD) have a high prevalence and in many patients pain and masticatory dysfunction persist despite a range of treatments. Non-invasive brain neuromodulatory methods, namely transcranial direct current stimulation (tDCS), can provide relatively long-lasting pain relief in chronic pain patients.

Objective: To define the neuromodulatory effect of five daily 2x2 motor cortex high-definition tDCS (HD-tDCS) sessions on clinical pain and motor measures in chronic TMD patients.

Excitatory and inhibitory brain metabolites as targets of motor cortex transcranial direct current stimulation therapy and predictors of its efficacy in fibromyalgia.

Objective: Transcranial direct current stimulation (tDCS) has been shown to improve pain symptoms in fibromyalgia (FM), a central pain syndrome whose underlying mechanisms are not well understood. This study was undertaken to explore the neurochemical action of tDCS in the brain of patients with FM, using proton magnetic resonance spectroscopy (1H-MRS).

Methods: Twelve patients with FM underwent sham tDCS over the left motor cortex (anode placement) and contralateral supraorbital cortex (cathode placement) for 5 consecutive days, followed by a 7-day washout period and then active tDCS for 5 consecutive days.

μ-Opioid activation in the midbrain during migraine allodynia - brief report II.

We investigated in vivo the allodynic response of the central μ-opioid system during spontaneous migraine headaches, following a sustained pain threshold challenge on the trigeminal ophthalmic region. Six migraineurs were scanned during the ictal and interictal phases using positron emission tomography (PET) with the selective μ-opioid receptor (μOR) radiotracer [11C]carfentanil. Females were scanned during the mid-late follicular phase of two separate cycles.

Association of μ-Opioid Activation in the Prefrontal Cortex with Spontaneous Migraine Attacks - Brief Report I.

We evaluated the μ-opioid system during spontaneous episodic migraine headaches. Seven patients were scanned at different phases of their migraine using Positron Emission Tomography with the selective μ-opioid receptor (μOR) radiotracer [11C]carfentanil. In the ictal phase, there was μOR activation in the medial prefrontal cortex, which was strongly associated with the μOR availability level during the interictal phase.

Building up analgesia in humans via the endogenous μ-opioid system by combining placebo and active tDCS: a preliminary report.

Transcranial Direct Current Stimulation (tDCS) is a method of non-invasive brain stimulation that has been frequently used in experimental and clinical pain studies. However, the molecular mechanisms underlying tDCS-mediated pain control, and most important its placebo component, are not completely established. In this pilot study, we investigated in vivo the involvement of the endogenous μ-opioid system in the global tDCS-analgesia experience.

3D-neuronavigation in vivo through a patient's brain during a spontaneous migraine headache.

A growing body of research, generated primarily from MRI-based studies, shows that migraine appears to occur, and possibly endure, due to the alteration of specific neural processes in the central nervous system. However, information is lacking on the molecular impact of these changes, especially on the endogenous opioid system during migraine headaches, and neuronavigation through these changes has never been done. This study aimed to investigate, using a novel 3D immersive and interactive neuronavigation (3D-IIN) approach, the endogenous µ-opioid transmission in the brain during a migraine headache attack in vivo.

Migraine and the Mu-opioidergic system-Can we directly modulate it? Evidence from neuroimaging studies.

Migraine is a chronic trigeminal pain condition that affects the daily lives of a large part of our population. Its debilitating headache attacks, with increased sensitivity to multiple forms of stimuli, force many patients to rely on over the counter analgesics and resort to abuse of prescription medications, particularly opioid agonists. In the latter case, the indiscriminate medication-driven activation of the opioid system can lead to undesired side effects, such as the augmentation of hyperalgesia and allodynia, as well as the chronification of the attacks.

Real-time sharing and expression of migraine headache suffering on Twitter: a cross-sectional infodemiology study.

Background: Although population studies have greatly improved our understanding of migraine, they have relied on retrospective self-reports that are subject to memory error and experimenter-induced bias. Furthermore, these studies also lack specifics from the actual time that attacks were occurring, and how patients express and share their ongoing suffering.

Objective: As technology and language constantly evolve, so does the way we share our suffering.

Immediate effects of tDCS on the μ-opioid system of a chronic pain patient.

We developed a unique protocol where transcranial direct current stimulation (tDCS) of the motor cortex is performed during positron emission tomography (PET) scan using a μ-opioid receptor (μOR) selective radiotracer, [(11)C]carfentanil. This is one of the most important central neuromechanisms associated with pain perception and regulation. We measured μOR non-displaceable binding potential (μOR BP(ND)) in a trigeminal neuropathic pain patient (TNP) without creating artifacts, or posing risks to the patient (e.